The committee considered reports and presentations from Canadian scientists on oculorespiratory syndrome (ORS) - a newly reported complication of vaccination with inactivated influenza vaccine. The syndrome, first reported in Canada in 2000, consists of one or more of the following: red eyes, acute respiratory symptoms (including respiratory distress, throat tightness and/or chest discomfort), and facial oedema. There may or may not be associated systemic symptoms, including high fever. Symptoms vary from mild to severe, resolving fully within 48 hours. During the season 2000-2001, 96% of reported cases were linked to the vaccine produced by one of two vaccine manufacturers with products licensed and distributed in Canada for that season.
Characteristically, the onset of symptoms is 2-24 hours after immunization, more commonly in women than in men, and particularly in the age group 40-59 years. First-time recipients and subjects with an allergic predisposition are especially susceptible. It is not clear why there is special predisposition in these subjects. An investigation into the manufacturing process and transmission electron microscopy of the vaccine material found that there was variation in the process of disaggregation of virion particles, resulting in a disproportionate number of unsplit virion aggregates in the implicated product. When a change in the manufacturing process was made in the 2001 vaccine product that resulted in a reduced number of large aggregates, there were subsequently fewer and milder cases of ORS being reported. Cases of ORS were reported in the 2001 vaccination campaign for both vaccines, and people affected previously appeared to have a relatively higher risk of recurrence with revaccination.
While the pathogenesis of ORS is not understood, various theories have been suggested. The reaction is not anaphylactic, and although an immunological mechanism has been proposed, its nature is not defined.
It was also discovered that a similar, albeit smaller, series of adverse events had occurred in association with another influenza vaccine produced by a different manufacturer in Europe in 1995-1996.
The issue of ORS, added to previous safety concerns related to a novel intranasal influenza vaccine, raises concerns regarding the evaluation and regulatory control of influenza vaccines. Manufacturing changes according to the prevailing antigenic profile of the virus commonly happen in a short time interval. When such changes might have implications for safety, this would best be detected by a sound system of safety surveillance and rapid response on the part of the regulatory authority. GACVS resolved to look into the special issues that are necessary to ensure enhanced safety of influenza vaccines.